The specific association of biological macromolecules is fundamental to all living systems. The recognition and combination of two such molecules depends on the three-dimensional structures of each of them. We propose to determine by single crystal x-ray crystallography the tertiary structures of macromolecules which combine specifically with other macromolecules. We have chosen to focus on two different problems of macromolecule recognition and association. One is the agglutination of certain cell surfaces by plant lectins. This study has led to the determination of the structure of wheat germ agglutinin. Current and proposed work is directed toward finding the sites on this molecule which bind to groups of sugars attached to cell surfaces. An unusual internal structural redundancy has already suggested the orientations which agglutinated groups bear to one another. The second problem which we are studying is the nature of the recognition of specific tRNA by its cognate aminoacyl-tRNA-ligase, an early step of protein synthesis. We have determined the structure of a ligase to 5.5 A resolution and are extending this to higher resolution. We are also determining the structure of a tRNA non-cognate to our ligase and actively seeking to crystallize others. Direct knowledge of the structure of the specific complex between macromolecules is the most unambiguous path to a detailed understanding of the specificity of the interaction. We are seeking to obtain such complexes of these and other systems as single crystals, but in lieu of them we continue work on the components individually. Reconstruction of the complex from its components requires extensive model building and essential information about their behavior in solution.